Human intraepithelial lymphocytes (IEL) and intestinal epithelial cells (EC) make up the barrier between the intestinal lumen (containing myriads of antigens) and the lamina propria (containing a rich network of immune cells). Since IEL and EC both have unique functional characteristics, the interaction between these two cell types may be essential for the maintenance of the unique immune microenvironment of the intestine. This interaction will be evaluated in three parts. The models for EC will be either fresh colonic EC or a malignant colonic (adenocarcinoma) cell line called DLD01. First, the mechanism by which IEL bind to EC will be studied. IEL have a much greater propensity to bind to DLD-1 monolayers than do peripheral blood (PB) CD8+ T lymphocytes. Such studies may indicate what cell surface structures on IEL account for this binding. Second, experiments will determine whether EC have stimulatory or suppressive effects on IEL or on PB CD8+ T lymphocyst. For example, do EC activate and trigger the proliferation of IEL, or in contrast, do EC induce IEL to become suppressor cells that inhibit B cell immunoglobulin synthesis or T cell proliferation? These studies will indicate what general modulatory effects the EC may have on the IEL. Finally, the cytotoxic activities of IEL against EC will be investigated. IEL will be tested for their ability to carry out a range of lytic activities. Those most potent activities will be further investigated to determine, for example, the phenotype of the precursor and effector cells. Human IEL are a little-understood compartment of lymphocytes whose interactions with EC have never been studied. Yet, these interactions may be critical to the mucosal immune network.